Nakajima H, Fujiwara H, Takai Y, Izumi Y, Sano S, Tsuchida T, Hamaoka T
J Immunol. 1985 Sep;135(3):2199-205.
In the present study we investigated some of the cellular mechanisms for the generation of macrophage-activating factor(s) (MAF) in immune responses to tumor antigens. C3H/HeN mice were immunized to syngeneic MH134 hepatoma or MCH-1-A1 fibrosarcoma by intradermal inoculation of viable tumor cells, followed by the surgical resection of the tumor. Spleen and lymph node cells from these tumor-immune mice were stimulated in vitro with the corresponding tumor cells, and supernatant from such a culture was tested for an ability to activate macrophages to exert their cytostatic and cytolytic activities as detected on tumor cells unrelated to immunizing tumors. Peritoneal adherent cells as a macrophage source, which were preincubated with supernatant from co-culture of tumor-unimmunized normal spleen and lymph node cells plus tumor cells, failed to exhibit any significant antitumor effect on unrelated X5563 tumor cells, whereas the addition of supernatant from cultures containing immune lymphocytes to adherent cells resulted in appreciably potent cytostatic and cytolytic effects on X5563 tumor cells, indicating the generation of MAF in culture supernatant. The activation of tumor-immune spleen and lymph node cells for MAF generation was tumor-specific, because anti-MH134- and anti-MCH-1-A1-immune lymphocytes produced MAF by the stimulation with the respective but not with the other alternative tumor cells. Such MAF production was abolished by treatment of tumor-immune spleen and lymph node cells with anti-Thy-1.2 or anti-Lyt-1.1 but not with anti-Lyt-2.1 antibody plus complement before culturing. These results indicate that the tumor-specific Lyt-1+2- T cell subset has a crucial role in generating MAF by which an adherent cell population as a source of macrophages acquires the potential for inducing a cytolytic as well as a cytostatic effect on tumor cells.
在本研究中，我们调查了在针对肿瘤抗原的免疫反应中产生巨噬细胞激活因子（MAF）的一些细胞机制。通过皮内接种活肿瘤细胞免疫C3H/HeN小鼠，使其对同基因的MH134肝癌或MCH-1-A1纤维肉瘤产生免疫反应，随后进行肿瘤的手术切除。用相应的肿瘤细胞体外刺激这些肿瘤免疫小鼠的脾细胞和淋巴结细胞，并检测这种培养物的上清液激活巨噬细胞以发挥其对与免疫肿瘤无关的肿瘤细胞的细胞抑制和细胞溶解活性的能力。作为巨噬细胞来源的腹腔贴壁细胞，预先与未免疫肿瘤的正常脾细胞和淋巴结细胞加肿瘤细胞共培养的上清液孵育，对无关的X5563肿瘤细胞未表现出任何显著的抗肿瘤作用，而向贴壁细胞中添加含有免疫淋巴细胞的培养物的上清液，则对X5563肿瘤细胞产生明显有效的细胞抑制和细胞溶解作用，表明培养上清液中产生了MAF。肿瘤免疫脾细胞和淋巴结细胞产生MAF的激活是肿瘤特异性的，因为抗MH134和抗MCH-1-A1免疫淋巴细胞分别受到各自而非其他替代肿瘤细胞的刺激时产生MAF。在培养前用抗Thy-1.2或抗Lyt-1.1抗体而非抗Lyt-2.1抗体加补体处理肿瘤免疫脾细胞和淋巴结细胞，可消除这种MAF的产生。这些结果表明，肿瘤特异性的Lyt-1 + 2 - T细胞亚群在产生MAF中起关键作用，通过MAF，作为巨噬细胞来源的贴壁细胞群体获得了对肿瘤细胞诱导细胞溶解以及细胞抑制作用的潜力。
